Evidence suggests that fish are more tolerant than mammals to imbalanced dietary amino acid profiles. However, the behavioral and physiological responses of fish to individual deficiencies in dietary indispensable amino acids (IDAA) remain unclear. This study examined how stomachless fish respond to diets deficient in limiting IDAA (lysine, methionine, and threonine), using Zebrafish (Danio rerio) as a model. The response to deficient diets was assessed based on; 1) growth performance and feeding efficiency; 2) feed intake; 3) expression of appetite-regulating hormones and nutrient-sensing receptors; and 4) muscle postprandial free amino acid (FAA) levels. There were 6 treatments, each with 3 replicate tanks. A semi-purified diet was formulated for each group. The CG diet was based on casein and gelatin, while the FAA50 diet had 50 % of dietary protein supplied with crystalline amino acids. Both were formulated to contain matching, balanced amino acid profiles. The remaining diets were formulated the same as the FAA50 diet, with minor adjustments to create deficiencies in selected IDAA. The (-) Lys, (-) Met, and (-) Thr diets had lysine, methionine, and threonine withheld from the FAA mix, respectively, and the Def diet was deficient in all three. The juvenile Zebrafish were fed to satiation 3 times daily from 21 to 50 days-post-hatch. Results showed that 50 % replacement of dietary protein with crystalline amino acids significantly reduced growth of juvenile Zebrafish. There were no significant differences in growth between the FAA50 group and groups that received deficient diets. The deficiency of singular IDAA did not induce significant changes in feed intake; however, the combined deficiency in the Def diet caused a significant increase in feed intake. This increased feed intake led to decreased feeding efficiency. A significant decrease in feeding efficiency was also observed in the (-) Lys group. There was an observed upregulation of neuropeptide Y (NPY), an orexigenic hormone, in the Def group. Overall, results from this study suggest stomachless fish increase feed intake when challenged with IDAA-deficient diets, and the regulation of NPY might play a role in this response.

2024-10-01·European Heart Journal - Case Reports

A case report: pitfalls in antibacterial therapy with rifampicin for mechanical valve endocarditis—the king of drug interactions

Article

作者: Higaki, Takashi ; Honda, Ryosuke ; Yamaguchi, Osamu ; Akazawa, Yusuke ; Inoue, Katsuji

AbstractBackgroundRifampicin is a strong inducer of the hepatic cytochrome P450 (CYP) family and is known to interact with many clinical drugs. However, to our knowledge, no case of worsening heart failure (HF) due to the interaction between rifampicin and HF drugs has been reported.Case summaryA 32-year-old female, who had undergone intracardiac repair for an incomplete atrioventricular septal defect with dextrocardia and prosthetic valve replacements for right and left atrioventricular valve regurgitation, presented as an outpatient. Her medications included tolvaptan 15 mg and warfarin 1.25 mg. She had a slight fever and Osler nodes at her fingers. Blood culture bottles grew methicillin-resistant Staphylococcus epidermidis, and several vegetations were observed on the right atrioventricular mechanical valve with a transoesophageal echocardiogram. She was diagnosed with prosthetic valve endocarditis and treated with antibiotic agents including rifampicin. After a week, she developed systemic oedema and had a marked decrease in prothrombin time–international normalized ratio (PT-INR). Rifampicin was promptly discontinued due to a strong suspicion of a drug–drug interaction. Consequently, both her congestion and the PT-INR stabilized, and she was discharged after 8 weeks of antibiotic treatment.DiscussionThe introduction of rifampicin induces CYP family members such as CYP3A4 and CYP2C9. Warfarin is metabolized by CYP2C9 and tolvaptan is also metabolized by CYP3A4, resulting in a notable reduction of their blood levels when co-administered with rifampicin. The clinical challenges arising from interactions between HF drugs and rifampicin can be categorized into two main groups: worsening HF and thrombotic complications. Clinicians should remain vigilant and informed about these potential issues.

2024-10-01·Surgical Infections

Classification and Risk Factors for Surgical Site Infections in Radical Cystectomy: A 16-Year Analysis

Article

作者: Hesse, David G. ; Smani, Shayan ; Rahman, Syed N. ; Lokeshwar, Soum D. ; Choksi, Ankur U. ; Martin, Thomas V. ; Ip, Kevan L. ; Leapman, Michael S. ; Javier-DesLoges, Juan F.

Introduction: Surgical site infection (SSI) is a substantial cause of peri-operative morbidity among patients undergoing radical cystectomy (RC). The purpose of this study was to identify the risk factors of SSI after RC and to classify and characterize treatment of SSIs. Methods: We retrospectively analyzed peri-operative characteristics and SSI, for patients undergoing RC from 2007 to 2022. Patients were stratified by SSI versus no SSI and differences were assessed. Uni-variable/multi-variable logistic regression analyses were performed to identify factors associated with SSI. SSIs were categorized by the Centers for Disease Control and Prevention (CDC) type: Superficial incisional, deep incisional, and organ/space confined. Results: Three hundred and ninety-eight patients had RC, 279 open, and 119 robotic; 78 (19.6%) developed SSI. Cohorts were similar demographically. Length of stay (LOS) was longer in the SSI cohort (8.8 d versus 12.4 d, p < 0.001), and body mass index (BMI) was greater in patients with SSI (24.34 vs. 25.39, p = 0.0003). On uni-variable analysis, age, gender, Charlson Comorbidity Index, diabetes mellitus, diversion, odds ratio (OR) time, blood loss, and open versus robotic technique were not substantial SSI predictors. BMI was an independent risk factor for SSI on both uni-variable (OR: 1.07, 95% confidence interval [CI]: 1.018-1.115, p = 0.0061) and multi-variable analysis (OR: 1.06, 95% CI: 1.009-1.109, p = 0.02) for 10 (12.8%) and 24 (30.8%) superficial and deep-incisional SSIs, respectively. Superficial wound SSI was treated conservatively with 60% receiving antibiotic agents and no procedural intervention. Deep SSIs received antibiotic agents and 50% required surgical intervention. There were 44 (56.4%) organ/space SSIs, and the most common treatment was antibiotic agents (100%) and IR drain placement (30, 68.2%). Conclusion: In patients undergoing RC, BMI was an independent risk factor for SSI. Type of the surgical procedure, robotic versus open, was not predictive of SSI. LOS was longer for patients with SSI. SSI was managed differently depending on CDC classification.

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